Light and electron microscope immunocytochemistry will be used to localize carbonic anhydrase in osteoclasts from normal, untreated mice and from normal mice treated with calcitonin to inactivate and with parathyroid hormone to activate osteoclastic bone resorption. Cells from normal animals will serve as controls for comparison with osteoclasts from grey-lethal mutant mice. Grey-lethal mutant mice have been used as models for human osteopetrosis. Osteopetrotic mice and humans show symptoms of defective tooth eruption, defective dentition and defective craniofacial development. Unusual localizations or amounts of carbonic anhydrase in osteoclasts from the inner surfaces of the cranial bones of grey-lethal mutants may help to explain defects in tooth eruption in the maxilla and help to explain defects in craniofacial development. Antiserum will be made in rabbits using the high activity isoenzyme of mouse red blood cells. Acid secretion in the ruffled borders and lysosomes of osteoclasts, possibly controlled by carbonic anhydrase activity, will be detected with acridine orange fluorescence. Finally, an attempt will be made to develop a new, reliable histochemical method for carbonic anhydrase based on the ability of carbonic anhydrase to hydrolyze artificial substrates.